The acute gastric toxicity of acrylic acid esters was studied in F344 male rats. Gavage administration of a single dose of ethyl acrylate (EtAc) or methyl acrylate (MeAc) caused dose- and time-dependent mucosal and submucosal edema and vacuolization of the tunica muscularis in the forestomach and submucosal edema in the glandular stomach. Equivalent sc or ip doses of EtAc did not produce similar gastric lesions. Structure-toxicity relationships revealed that MeAc was a more potent gastric toxin than EtAc, while acrylic acid and n-butyl acrylate were without effects. Gavage administration of equimolar doses of the saturated analoges of acrylic acid esters (methyl propionate or ethyl propionate) as well as methacrylic acid esters were without gastric toxicity. The gastric toxicity of acrylic acid esters was found to be dependent upon both acrylate ester concentration in dose vehicle and the lipophilicity of the dose vehicle (corn oil vs water). Gavage administration of 14 consecutive daily doses of EtAc produced no lesions in the glandular stomach, which indictes that prolonged insult with EtAc resulted in adaptation of the glandular stomach. One the other hand, similar treatment with EtAc caused a dose-dependent mucosal edema associated with vesicles, mucosal hyperplasia and hyperkeratosis, submucosal edema and inflammation, vacuolization of tunica muscularis and mucosal erosions or ulcers.